CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：A bispecific nanosystem activates endogenous natural killer cells in the bone marrow for haematologic malignancies therapy.
A bispecific nanosystem activates endogenous natural killer cells in the bone marrow for haematologic malignancies therapy.
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血液系统恶性肿瘤通常起源于骨髓病变，但目前尚无针对该部位肿瘤细胞的有效靶向疗法。在此，我们构建了一种骨髓靶向纳米系统CSF@E-Hn，其基于造血干细胞来源的纳米囊泡，表面修饰有抓取配体（aPD-L1和aNKG2D），并封装集落刺激因子（CSF），用于治疗血液系统恶性肿瘤。CSF@E-Hn靶向骨髓，并借助抓取配体将肿瘤细胞与NK 细胞拉近，激活后者以实现对肿瘤细胞的特异性靶向和清除。治疗疗效在急性髓系白血病和多发性骨髓瘤小鼠模型中得到验证。对治疗后骨髓微环境的综合评估显示，将CSF整合入骨髓靶向纳米系统可促进造血干细胞分化、增强记忆T细胞生成并维持骨稳态，且能长期预防复发。我们的纳米系统为血液系统恶性肿瘤的治疗提供了一种有前景的策略。
Haematologic malignancies commonly arise from the bone marrow lesion, yet there are currently no effective targeted therapies against tumour cells in this location.
Here we constructed a bone-marrow-targeting nanosystem, CSF@E-Hn, which is based on haematopoietic-stem-cell-derived nanovesicles adorned with gripper ligands (aPD-L1 and aNKG2D) and encapsulated with colony-stimulating factor (CSF) for the treatment of haematologic malignancies. CSF@E-Hn targets the bone marrow and, thanks to the gripper ligands, pulls together tumour cells and natural killer cells, activating the latter for specific tumour cell targeting and elimination.
The therapeutic efficacy was validated in mice bearing acute myeloid leukaemia and multiple myeloma. The comprehensive assessment of the post-treatment bone marrow microenvironment revealed that the integration of CSF into a bone-marrow-targeted nanosystem promoted haematopoietic stem cell differentiation, boosted memory T cell generation and maintained bone homoeostasis, with long-term prevention of relapse.
Our nanosystem represents a promising strategy for the treatment of haematologic malignancies.
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